(99m)Tc-labelled nanosystem as tumour imaging agent for SPECT and SPECT/CT modalities

Int J Pharm. 2013 Jun 5;449(1-2):10-7. doi: 10.1016/j.ijpharm.2013.03.049. Epub 2013 Apr 2.


We report the synthesis, in vitro and in vivo investigation of folate-targeted, biocompatible, biodegradable self-assembled nanoparticles radiolabelled with (99m)Tc, as potential new SPECT or SPECT/CT imaging agent. Nanoparticles with hydrodynamic size in the range of 75-200 nm were prepared by self-assembly of chitosan and folated poly-γ-glutamic acid, and then radiolabelled with (99m)Tc. The nanoparticles target tumour cells overexpressing folate receptors and internalize specifically into them to realize early tumour diagnosis detected by SPECT and SPECT/CT modalities. Rat hepatocellular carcinoma cells were used as model system. Cell specificity and tumour targeting efficacy of these nanosystems were investigated in vitro, and in vivo using SPECT and fusion nanoSPECT/CT imaging. In vitro results showed that the radiolabeled nanosystem was efficiently internalized by tumour cells. Whole-body biodistribution of the new radiolabelled, folate-targeted nanoparticles revealed higher uptake in the tumorous kidney compared to the non-tumorous contralateral side. Uptake by the lungs and thyroids was negligible, which confirmed the stability of the nanoparticles in vivo. In vivo SPECT and SPECT/CT imaging visually reinforced the uptake results and were in accordance with the biodistribution data: the new nanoparticles as a targeted contrast agent improve tumour targeting and are able to detect folate-receptor-overexpressing tumours in animal models with enhanced contrast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / pathology
  • Chitosan / chemistry
  • Folate Receptors, GPI-Anchored / metabolism
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / pathology
  • Male
  • Nanoparticles
  • Particle Size
  • Radiopharmaceuticals* / pharmacokinetics
  • Rats
  • Rats, Inbred F344
  • Sodium Pertechnetate Tc 99m* / pharmacokinetics
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon / methods
  • Tomography, X-Ray Computed / methods


  • Folate Receptors, GPI-Anchored
  • Radiopharmaceuticals
  • Chitosan
  • Sodium Pertechnetate Tc 99m